Understanding How Cancer Grows

Most cells in our bodies divide to grow or to replenish lost cells. Normally, these divisions occur in a regulated and ordered manner, but when it gets out of hand, these rapidly dividing cells become the foundation for tumor cells and lead to cancer. In the process, most of the fuel consumed is glucose, which is a form of sugar.

Scientists have long believed that the cell mass of new cells, including cancer cells, comes from glucose. However, a team of MIT biologists have found in a new study, published in Developmental Cell, that the largest source is not glucose but rather amino acids, a component that cells consume in smaller amounts.

Cancer cells differ from normal cells in how they generate energy. This phenomenon, known as the “Warburg effect,” shows that tumor cells use a less efficient process—called fermentation, which doesn't use oxygen—instead of the normal chemical reactions that human cells use to break down glucose. The end result is that cancer cells produce much less energy compared to that of normal cells.

One hypothesis to explain this less efficient strategy is that cancer cells might be using this alternative pathway to create building blocks for new cells; but this seems to be repudiated by observations that most of the glucose is converted to lactate, a waste product. In addition, minimal research has been conducted on the composition of new cancer cells or other rapidly dividing mammalian cells.

"Because mammals eat such a diversity of foods, it seemed like an unanswered question about which foods contribute to what parts of mass," says Matthew Vander Heiden, a member of MIT's Koch Institute for Integrative Cancer Research, and senior author of the study.

Determining the Building Blocks of Cancer
Cancerous cells. Image Credit: Morten Bjørklund

The researchers grew several different types of cancer cells and normal cells in culture dishes. By feeding these cultures different nutrients with varying forms of carbon nitrogen, they were able to track where the original molecules ended up within the cell—a simple technique that allowed the scientists to figure out where the building blocks were coming from. They also weighed the cells to calculate the percentage of the cell mass contributed by each molecule.

What they found was that despite the high consumption of both glucose and the amino acid glutamine, both of these contributed little to the cells' mass, with glucose accounting for 10 to 15 percent of the carbon in the cells, while glutamine contributed only 10 percent. Excluding glutamine, it was other amino acids—the basic building blocks of proteins—that were actually the largest contributors, generating 20 to 40 percent of carbon in the total mass.

"There's some economy in utilizing the simpler, more direct route to build what you're made out of," Vander Heiden says. After all, cells are mostly protein in composition.

While scientists still don't know why human cells consume so much glucose, the researchers found that most of the glucose was excreted as lactate. The team concluded that the high glucose consumption is not for manipulation of carbon but rather the energy it provides.

The researchers are now looking into further investigating how the Warburg effect may be helping the cells to reproduce. Their research provides a new way of looking at cancer cell metabolism, and it may lead to new drugs or treatments that will cut off the cells’ ability to divide.

"If you want to successfully target cancer metabolism, you need to understand something about how different pathways are being used to actually make mass," says Vander Heiden.


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